Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Astrocytoma

Disease Attributes

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Lomustine

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients undergo LITT at baseline and receive lomustine PO on day 1. Treatment with lomustine repeats every 42 days for up to 6 cycles in the absence of disease progression or unaccepted toxicity.

Laser Interstitial Thermal Therapy

Barbara J O'Brien

This phase II trial studies how well laser interstitial thermal therapy and lomustine work in treating patients with glioblastoma or anaplastic astrocytoma that has come back. Using laser to heat the tumor cells may help to kill them. Drugs used in chemotherapy, such as lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving laser interstitial thermal therapy and lomustine may work better in treating patients with glioblastoma or anaplastic astrocytoma.

PRIMARY OBJECTIVES:

I. Determine the disease control rate at 6 months in patients with recurrent glioblastoma or isocitrate dehydrogenase (IDH)-wildtype anaplastic astrocytoma treated with Laser Interstitial Thermal Therapy (LITT) at recurrence, followed by salvage chemotherapy.

SECONDARY OBJECTIVES:

I. Estimate overall survival (OS) of patients with recurrent glioblastoma, or isocitrate dehydrogenase (IDH)-wildtype anaplastic astrocytoma treated with LITT at tumor recurrence, followed by salvage chemotherapy.

II. Estimate time to progression (TTP) of patients with recurrent glioblastoma, or isocitrate dehydrogenase (IDH)-wildtype anaplastic astrocytoma that are treated with LITT at tumor recurrence, followed by salvage chemotherapy.

III. Analyze volumetric data consisting of thermal damage threshold lines and overall tumor volume to determine any role of 'extent of ablation' in outcomes (OS and/or TTP).

IV. Characterize the safety profile of LITT followed by treatment with lomustine chemotherapy in the recurrent disease setting, using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

V. Assess the long-term steroid requirements following LITT, compared to historical controls.

VI. Determine the radiographic evolution of LITT-treated glioblastoma over time, using conventional magnetic resonance imaging (MRI) (T1 pre and post-contrast images, T2-weighted images \[T2WI\], fluid attenuating inversion recovery \[FLAIR\] images) and advanced brain tumor imaging (ABTI) \[magnetic resonance (MR) perfusion \[dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL)\], MR-diffusion, and MR spectroscopy), to include quantitative tumor metrics (volumetric extent of ablation and Response Assessment in Neuro-Oncology \[RANO\] criteria).

VII. Analyze health care utilization as measured by length of hospital stay following LITT (including inpatient rehabilitation care).

VIII. Evaluate patients' functional status (using the Karnofsky performance score \[KPS\] and the occurrence of symptoms \[using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT\[English\])\] self-reporting tool), and correlate to disease progression and tolerance to treatment.

EXPLORATORY OBJECTIVES:

I. Identify correlative tumor and peripheral blood molecular markers that impact outcomes, etc, and identify inflammatory/immunologic markers to assess neoantigen expression, etc, if sufficient tissue is available.

II. Identify and characterize changes in tumor tissue following LITT, by analyzing and comparing pre- and post-procedure tissue samples, if sufficient tissue is available.

OUTLINE:

Patients undergo LITT at baseline and receive lomustine orally (PO) on day 1. Treatment with lomustine repeats every 42 days for up to 6 cycles in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up every 3 months.

Laser Interstitial Thermal Therapy and Lomustine in Treating Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma

Phase II Study of Laser Interstitial Thermal Therapy (LITT) in Recurrent Glioblastoma

Will be summarized using standard descriptive statistics, such as mean, standard deviation, median, and range for continuous variables, frequency and proportion for categorical variables. Correlation will be assessed among continuous variables using Pearson or Spearman correlation coefficient, whichever is appropriate. Association between categorical variables will be examined by Chi-Squared test or Fisher's exact test when appropriate. Wilcoxon rank-sum test or Kruskal-Wallis test will be used to examine the difference on continuous variables between or among patient's characteristic groups.

Stable Disease per RANO occurs if the patient does not qualify for response or progression and requires stable non enhancing lesions, same/lower dose of corticosteroids, and clinical stability.

Complete Response per RANO requires complete disappearance of all enhancing measurable and nonmeasurable disease for at least 4 weeks; no new lesions; and stable/improved nonenhancing lesions, off corticosteroids (or on physiologic replacement dose) and clinical improvement/stability. Partial Response per RANO requires ≥50% decrease of enhancing lesions compared with baseline, sustained for at least 4 weeks; no progression of nonmeasurable disease; no new lesions; stable/improved nonenhancing lesions, same/lower dose of corticosteroids not greater than the dose at time of the baseline scan and clinically improved/stable.

Progression disease per the Response Assessment in Neuro-Oncology (RANO) is defined by any of the following: ≥25% increase in the sum of the products of perpendicular diameters of enhancing lesions (compared with baseline if no decrease) on stable or increasing doses of corticosteroids; a significant increase in T2/FLAIR nonenhancing lesions on stable or increasing doses of corticosteroids compared with the baseline scan or the best response after initiation of therapy, not due to comorbid events; the appearance of any new lesions; clear progression of nonmeasurable lesions; or definite clinical deterioration not attributable to other causes apart from the tumor or to a decrease in the corticosteroid dose.

Will summarize the MDASI-BT at each time point using descriptive statistics and evaluate the change of MDASI-BT over time and its correlation with response and/or treatment tolerance using linear mixed models, where random effects will be used to account for within-subject correlations.

Safety and toxicity of LITT by determination of adverse events and surgical complications within 2 weeks of the procedure, plus an additional 4 weeks (to account for potential delayed inflammatory changes and initiation of subsequent treatment). Safety for LITT procedure will be defined as the absence of severe clinical toxicity as determined by the CTCAE version 4.0, within 6 weeks of the procedure, and/or absence of acute events (ie, significant hemorrhage or brain herniation) documented on imaging. Severe toxicity will also be defined as a drop of 20 points or more in KPS and not amenable to corticosteroids, and likely attributable to the procedure, or symptomatic hemorrhage, increased brain edema resulting in herniation/impending herniation, and/or significant neurologic decline not amenable to corticosteroids. Safety and toxicity will be reassessed again throughout the duration of the study.

Overall Survival (OS) is the time from initial tumor diagnosis (definitive surgical resection or biopsy) to death from any cause. Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on OS.

The length of hospital stay in days, weeks or months. Length of Hospital stay was summarized by using standard descriptive statistics, such as mean, standard deviation, median, and range for continuous variables, frequency and proportion for categorical variables.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Patients undergo LITT at baseline and receive lomustine PO on day 1. Treatment with lomustine repeats every 42 days for up to 6 cycles in the absence of disease progression or unaccepted toxicity.

Laser Interstitial Thermal Therapy: Undergo LITT

Lomustine: Given PO

Treatment (LITT, Lomustine)

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Barbara O'Brien, MD/Associate Professor, Neuro-Oncology

Progression Disease

Partial Response

Non Evaluable

Disease Control Rate at 6 Months

Time to Progression (TTP)

Long-term Steroid Requirements

MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Data

Number of Participants With Incidence of Toxicity (Significant Hemorrhage or Brain Herniation) Documented on Imaging

Spots Global Cancer Trial Database for idh family wildtype